Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada R2H 2A6.
Mitochondrion. 2011 Nov;11(6):845-54. doi: 10.1016/j.mito.2011.06.007. Epub 2011 Jul 2.
Diabetic neuropathy is a major complication of diabetes that results in the progressive deterioration of the sensory nervous system. Mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of the neurodegeneration observed in diabetic neuropathy. Our recent work has shown that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory neurons in streptozotocin (STZ) induced diabetic rodents. In neurons, the nutrient excess associated with prolonged diabetes may trigger a switching off of AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling leading to impaired peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression/activity and diminished mitochondrial activity. This review briefly summarizes the alterations of mitochondrial function and proteome in sensory neurons of STZ-diabetic rodents. We also discuss the possible involvement of AMPK/SIRT/PGC-1α pathway in other diabetic models and different tissues affected by diabetes.
糖尿病性神经病是糖尿病的一种主要并发症，会导致感觉神经系统的进行性恶化。线粒体功能障碍被认为在糖尿病性神经病中观察到的神经退行性变的发病机制中起重要作用。我们最近的工作表明，线粒体功能障碍发生在链脲佐菌素（STZ）诱导的糖尿病啮齿动物的背根神经节（DRG）感觉神经元中。在神经元中，与长期糖尿病相关的营养过剩可能会触发 AMP 激酶（AMPK）和/或沉默信息调节因子 T1（SIRT1）信号的关闭，导致过氧化物酶体增殖物激活受体 γ 共激活因子-1（PGC-1α）表达/活性受损和线粒体活性降低。本文简要总结了 STZ 糖尿病啮齿动物感觉神经元中线粒体功能和蛋白质组的改变。我们还讨论了 AMPK/SIRT/PGC-1α 通路在其他糖尿病模型和受糖尿病影响的不同组织中的可能参与。
